János Matkó Ph.D., D.Sc.


       

Short CV.:

Research interest:

Our earlier studies together with many others have shown that the plasma membrane of vertebrate cells is highly compartmented. This is due on one hand to the lipid raft membrane microdomains, and on the other hand to the dynamic coupling between the plasma membrane and cortical cytoskeleton. The exact properties of the membrane rafts, however, still remained partly controversial and unresolved. It is generally accepted that the sphingolipids/gangliosides may spontaneously segregate within the fluid bilayer and these clusters are further stabilized by cholesterol. This may end in formation of small, submicrometer size unstable domains, which may grow and expand to large scale signaling domains upon external stimuli received by the cell. The signaling rafts then may form larger, membrane attached complex units, such as “signalosomes” [Eggeling et al., Nature 2009. 457: 1159; Lingwood D, Simons K., Science 2010. 327: 46].

The mechanism and regulation of lipid raft formation still remained unclear, such as their functional role in the normal and pathological immune functions of lymphocytes. To investigate submicron organization levels of lipid microdomains we have developed/adopted several physical techniques for cellular systems, like fluorescence resonance energy transfer (FRET) analysis; flow cytometric differential detergent resistance analysis (FCDR); or the differential-polarization laser scanning confocal microscopy (DP-LSM) [Gombos et al, Cytometry 2004. 61:117; Bacsó et al, Cytometry 2004. 61:105; Szöllősi et al, Methods in Cell Biol. 2004. 75: 105-152.; Szentesi et al, Cytometry 2005. 67A: 119; Gombos et al, Cytometry 2008. 73: 220; Kiss et al, Cytometry 2008. 73: 599].

Currently our group is interested in revealing the factors controlling lipid raft organization in lymphocytes and phagocytes. The immune-regulatory role of steroid lipids (cholesterol and estradiols) in normal and pathological lymphocyte function is also in the focus of our research. Recently we prepared two monoclonal, IgG3-type cholesterol-specific antibodies [Biró et al, J Lipid Res 2007. 48: 19-29]. These mAbs proved to be useful as markers of membrane cholesterol in cells. In addition they were able to block in vitro HIV-1 infection and production of human macrophages and T cells [Beck et al, J Lipid Res 2010. 51:286-96] and to promote macrophage phagocytosis and T cell activation through modulation of antigen presentation [Izsépi et al, Immunol Lett 2012. 143:106-115]. The lipid rafts can also be specific targets of various microbes [Phogat et al, J Intern Med 2007:262, 26], especially if the receptors recognizing surface molecules of the microbes are raft-localized (e.g. HIV, influenza, measle viruses). This raises the possibility of inhibiting the infection by modulation of lipid rafts on target cells. The mechanism of modulatory action of our anti-cholesterol mAbs and the estradiol steroid lipids are currently in the focus of our investigations in the lab.

Communication of the immune cells can be realized in various forms (direct and indirect) and levels. A direct communication is the immunological synapse (IS). The contact structures often form in immune organs (mainly in lymph nodes) between antigen presenting cells (DCs, B cells, macrophages) and Th and Tc lymphocytes or between NK cells and their targets. The IS can be considered as an essential platform of T and NK cell activation [Manz BN, Groves JT: Nat Rev Mol Cell Biol. 2010. 11:342; Valitutti S, Dupré L: Curr Top Microbiol Immunol. 2010. 340:209]. Another new form of long range (up to 100 micrometer distance) direct coupling between immune cells are the so called “membrane nanotubes”. Such nanotubes can form between lymphocytes (B and T cells), between macrophages or dendritic cells, as well as between NK cells and their target cells [Önfelt et al: Science STKE 2005; Davis DM: Nat. Rev. Immunol. 2009. 9:543; Davis DM, Sowinski S: Nat. Rev. Mol. Cell. Biol. 2008. 9:431]. They show various morphologies and transport of molecules or even vesicles along the tube from one cell to another was also reported. Mechanistic details and regulatory factors of membrane nanotube formation are, however, very poorly understood, yet. Our lab is currently investigating the regulation of nanotube formation, the role of lipid rafts in it and the intercellular transport, as well as the contribution of myosin motor proteins to the growth and function of nanotube networks in lymphoid cells.

Membrane nanotube network between mature murine B cells (A) and between dividing B cells (B). (green: cholera toxinB-A488; red: CTXB-A647) (Izsépi et al, MAF12 Conference, 2011, Strasbourg, France)

Research projects

Methods/Experience

* The lab is an open cell analysis & sorting service unit to interested companies and academic sites (under supervision of the Faculty of Science of ELU)

Support:

Selected publications:

Links for all publications: MTMT